کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6021895 | 1580654 | 2014 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
RGS4 is involved in the generation of abnormal involuntary movements in the unilateral 6-OHDA-lesioned rat model of Parkinson's disease
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
6-OHDALID6-HydroxydopamineGPCRRGSRGS4Regulators of G-protein signallingG-protein coupled receptor - G-پروتئین همراه گیرندهAntisense oligonucleotides - oligonucleotide antisenseAIMS - اهدافParkinson's disease - بیماری پارکینسونabnormal involuntary movements - حرکات غیر دائمی غیر طبیعیL-DOPA-induced dyskinesia - دیسکینزی ناشی از L-DOPA
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
عصب شناسی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Regulators of G-protein signalling (RGS) proteins are implicated in striatal G-protein coupled receptor (GPCR) sensitisation in the pathophysiology of l-DOPA-induced abnormal involuntary movements (AIMs), also known as dyskinesia (LID), in Parkinson's disease (PD). In this study, we investigated RGS protein subtype 4 in the expression of AIMs in the unilateral 6-hydroxydopamine (6-OHDA)-lesioned rat model of LID. The effects of RGS4 antisense brain infusion on the behavioural and molecular correlates of l-DOPA priming in 6-OHDA-lesioned rats were assessed. In situ hybridisation revealed that repeated l-DOPA/benserazide treatment caused an elevation of RGS4 mRNA levels in the striatum, predominantly in the lateral regions. The increased expression of RGS4 mRNA in the rostral striatum was found to positively correlate with the behavioural (AIM scores) and molecular (pre-proenkephalin B, PPE-B expression) markers of LID. We found that suppressing the elevation of RGS4 mRNA in the striatum by continuous infusion of RGS4 antisense oligonucleotides, via implanted osmotic mini-pumps, during l-DOPA priming, reduced the induction of AIMs. Moreover, ex vivo analyses of the rostral dorsolateral striatum showed that RGS4 antisense infusion attenuated l-DOPA-induced elevations of PPE-B mRNA and dopamine-stimulated [35S]GTPγS binding, a marker used for measuring dopamine receptor super-sensitivity. Taken together, these data suggest that (i) RGS4 proteins play an important pathophysiological role in the development and expression of LID and (ii) suppressing the elevation of RGS4 mRNA levels in l-DOPA priming attenuates the associated pathological changes in LID, dampening its physiological expression. Thus, modulating RGS4 proteins could prove beneficial in the treatment of dyskinesia in PD.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Disease - Volume 70, October 2014, Pages 138-148
Journal: Neurobiology of Disease - Volume 70, October 2014, Pages 138-148
نویسندگان
Wai Kin D. Ko, Marie-Laure Martin-Negrier, Erwan Bezard, Alan R. Crossman, Paula Ravenscroft,